Blood processing systems are used for a range of purposes. They are used, for example, to collect blood from donors, for autotransfusion where blood lost by a patient during an operation is collected, cleaned and reintroduced into the patient""s circulatory system, to prepare collected blood for freezing, to deglycerolize frozen thawed red cells, for washing red blood cells and for washing frozen thawed platelets.
There are features which would be very desirable with virtually all blood processing systems but are not provided by current systems. To understand these desirable features one must first fully appreciate the practical aspects of the blood processing technology as discussed below. The desirable features are small size of equipment, acceptably priced disposables, automatic operation, protection from operator error, protection from equipment error, speed of operation and complete one-step processing.
Considering first a blood collection system, the collection of blood from donors takes place both at blood banks and via use of mobile units during so-called blood drives with the mobile unit collection often exceeding that at the blood banks. Accordingly, it is desirable to have relatively compact systems so that a larger number can be easily transported to the site of blood collection. Fast blood collection is desirable since if donor comfort is increased by reducing the donation time it is easier to attract donors.
Whole blood has usually been collected from a donor via gravity flow; alternatively, use of a blood removal roller pump has been used to aid collection from a donor. The whole blood was then transported to a blood processing facility and centrifuged to separate the plasma from the erythrocytes. In some instances a leukocyte filter was used on the whole blood or on red cells to reduce the chance for undesirable patient reactions to donor leukocytes when donor red cells were later transfused into a patient. This whole blood collection procedure suffers from a number of drawbacks. One major drawback is that the procedure is highly dependent on the skill of the operator taking the blood donation, thus requiring extensive and expensive training of operators. Also, the current procedures require nearly constant operator attention, thereby limiting the amount of blood which can be safely collected in a given time period; i.e., the operator can only safely oversee a limited number of blood donations at any one time. There is also a drawback that having several people handle the whole blood as it is collected and separated into its component parts increases the chance of operator error. Another drawback is that the several steps required, even if carried out by a single operator, increase the risk of contamination of the whole blood and of its separated component parts.
An apparatus has also been proposed which has the capability of fully processing blood at the collection site but it is relatively bulky and requires the use of a built in rotating centrifuge. The apparatus has a number of limitations which include cost, relative bulkiness, the possibility of leaks at rotating seals, relatively slow speed since all blood must be collected prior to the beginning of separation into components, etc., and the requirement of close operator supervision. The apparatus is disclosed in U.S. Pat. Nos. 5,651,766; 5,728,060; and 5,733,253.
Another blood processing system, called an intraoperative autotransfusion system, is commonly used during certain operations, such as orthopedic surgery and open-heart surgery, when a great deal of blood can be lost by the patient. In autotransfusion the lost (shed) blood along with air, particulate matter and diluting solvents are collected. The air, solvents, and particulate matter are removed. The cells are washed and the hematocrit is increased to a desired level such as that normally present in the body (about 40%). The resulting blood cell suspension is transfused back into the patient. Autotransfusion reduces the cost and problems (incompatibility and infection) associated with blood bank blood. It would be desirable to have a relatively small size unit since operating rooms constitute a highly crowded environment. Furthermore, automatic operation is desirable as it allows medical personnel to attend to other matters while the autotransfusion unit carries out the desired task of collecting and cleansing red blood cells for re-infusion. Low cost of disposables is necessary since if the cost is too high even the technically best available system may not be used. The system set forth in U.S. Pat. Nos. 5,242,384 and 5,423,738 is adapted for automated autotransfusion but the high cost of the complex disposable and its tangential flow separator has prevented this system from wide commercial acceptance.
Another type of blood processing system is the thawed blood processing system. It is intended to remove glycerol and free plasma hemoglobin from thawed frozen red blood cells. It is primarily used by the military on land and aboard ship to provide red cells in emergency situations. The military has stockpiled a large number of units of blood, all of one universal donor type, for this purpose. Frozen blood is also commonly used when a patient undergoing elective surgery desires to stockpile his or her own blood for use during the surgery. Frozen blood is also used to supply rare blood types.
One of the problems with using frozen blood is that it requires that some type of agent be added to the red blood cells to allow them to be safely frozen; glycerol has commonly been used for this purpose. Also, some red blood cells are damaged by the freezing process. Once thawed, these damaged red blood cells release free plasma hemoglobin. Both the glycerol and free plasma hemoglobin must be reduced to safe levels in the thawed blood and saline and a red cell storage solution must be added to the thawed blood before transfusion into a patient. Once again, small size, automatic operation and low cost are important factors.
Another blood processing system is used for washing red blood cells. Blood is collected, separated into its components and concentrated red blood cells are stored in a bag which contains the storage solution to preserve the red cells. Once again, small size, automatic operation and low cost are important factors.
A further blood processing system is used to wash frozen thawed platelets. In this system the platelets are frozen with, for example, DMSO, and possibly other preservatives. When the frozen platelets are thawed, the DMSO and possibly other preservatives are preferably washed from the platelets before the platelets can be used.
U.S. Pat. Nos. 5,670,312; 5,460,493; 5,311,908; 5,273,517; 5,195,960; 4,985,153; and 4,385,630 disclose various types of blood processing systems and system components.
One aspect of the present invention is directed to a blood processing system designed for the automatic or semi-automatic processing of blood during processing procedures such as blood collection from a donor, intraoperative autotransfusion, thawed red blood cells processing, washing fresh red blood cells, and washing thawed platelets. The system provides for the use of an easily removable and replaceable cassette which contains all of the disposable components.
The blood processing system includes a housing having a panel; user controls are preferably mounted to the panel. The system also includes a cassette assembly mounted to the housing adjacent to an access opening in the panel for movement between a use position, adjacent to and covering the access opening, and a cassette-replacement position. The cassette assembly includes a cassette holder and cassette removably mounted to the holder. The cassette includes a cassette body having one or more through-holes. The cassette also includes flow channels defined at least in part by tubing, the tubing having first and second portions aligned with the through-holes. The cassette preferably carries all of the disposable elements, such as filter, separator, and tubing.
The system also includes a fastening assembly, typically a door, movably mounted to the housing for movement between a latched position, capturing the cassette between the panel and the door, and a released position. In an embodiment of the invention the door has roller tracks positioned to engage the first tubing portion when the cassette assembly is in the use position and when the door is in the latched position. A roller pump drive assembly is mounted within the housing and includes independently-driven roller assemblies. Each roller assembly includes a number of circumferentially positioned rollers. Each roller assembly is preferably mounted for rotation about a common axis. Each roller assembly is located to be aligned with the access opening and aligned with a corresponding first tubing portion. The first tubing portions in this embodiment are captured between the roller tracks on the door and the roller assemblies so that fluid is pumped through the first tubing portions by rotation of the roller assemblies.
A number of movable pinch elements are mounted within the housing and are aligned with the second tubing portions. The pinch elements are movable to selectively pinch the second tubing portions against the door, thus closing the tubing, when the door is in the latched position. A controller is operably coupled to the operator controls, roller pump drive assembly, cassette assembly and pinch elements.
A blood processing system made according to an embodiment of the invention is preferably designed so that the pumping rate and pumped volume are controlled by monitoring the pressure or other parameters within the system. When the system is used to pump blood from a donor, it is desired to pump the blood from the donor as fast as possible without harming the donor, such as collapsing a blood vessel, or damaging the blood being withdrawn. With the present invention the pumping rate of blood pumped from a donor can be determined and controlled by, for example, monitoring the drop in pressure along a portion of the flow path within the system and adjusting the pump speed to achieve a desired pressure level. By doing so, the pumping pressure can be maintained in an optimal range for a donor so that the vessel is not collapsed.
The system can be designed to automatically collect blood and shut down after collecting a chosen volume.
The hollow fiber separator is used to separate fluid from a cellular suspension (blood or blood components) flowing through it. A preferred hollow fiber separator includes a number of microporous hydrophilic hollow fibers arranged in a bundle of parallel fibers. The porous walls of these fibers have pore size that on average is about 0.2 to 0.5 microns in diameter. The fiber bundle is placed in a housing that closely surrounds the outside of this bundle. The ends of this bundle are potted and sealed with a liquid material such as polyurethane that solidifies and fills the spaces between the housing and all of the fibers. Each end of the bundle is then cut through the potting material at the ends of the housing. This exposes the lumens of the fibers. End caps are secured and sealed to each end of the housing. A port in each end cap leads fluid into or out of the chamber formed by the inside of the end cap and the cut ends of the fibers. Fluid containing cells (red cells or platelets) flows in one end cap, through the lumens of the fibers, and out the other end cap. A port in the wall of the housing is used to remove fluid which passes through the pores of the fibers from the outside surfaces of the fibers. This removed fluid typically comes from the fluid flowing through the lumens of the fibers. The removed fluid consists of a liquid containing salts, free plasma hemoglobin, possibly anticoagulant, possibly glycerol, other dissolved matter, and small particulates. The removal process is called tangential or cross-flow separation. The high velocity of flow inside the fibers keeps cells and other material away from the wall and prevents pore plugging or layering that can decrease removed fluid flow rates. The pressure levels at the end cap entrance and exit of the separator and at the removed fluid port affect removed fluid flow rate. A pump can be used to control this flow rate. Increases in the pressure differential across the fiber wall can increase removed fluid flow rate up to the point that significant and undesirable cellular layering occurs on the inside surfaces of the fibers which reduces removed fluid flow rate. The pressure differential and blood flow rate are controlled to prevent this.
When whole blood is concentrated by a hollow fiber separator and separated into red cells and plasma, plasma is the removed fluid. A recirculation process is preferably used to concentrate the red cells to a high hematocrit and to separate the plasma into a bag.
The washing of red cells or platelets preferably occurs by separating the removed fluid or waste from the cells with waste fluid flowing through the walls of the hollow fibers, out the plasma port, and into a waste bag. Saline or another solution is added at the cellular flow exit of the separator at a flow rate essentially equal to the waste flow. The saline is made to mix well with the cellular flow in a mixing tee and tubing. Then the cellular flow enters into the recirculation bag, goes inside the recirculation bag, goes out of the recirculation bag, and enters into the separator at a constant hematocrit, perhaps 45%. The recirculation bag can be mixed by mechanical manipulation to ensure a constant hematocrit is maintained in the bag and that the concentration of removed matter (e.g. free plasma hemoglobin; anticoagulant; glycerol) is uniform within the recirculation bag to ensure consistent performance. The wash process is then a continuous waste removal and saline or wash fluid replacement process that rapidly decreases the concentration of removed matter in the recirculation bag. Higher recirculation bag hematocrits, higher cellular fluid flow rates, and higher changes in hematocrit across the separator tend to improve the efficiency and speed of removal.
The most expensive component of the cassette is typically the plasma separator, such as a hollow fiber separator. One of the primary aspects of the invention is the recognition that a less expensive separator can be used if the system is designed so that blood can be selectively recirculated to pass all or part of the blood through the separator more than once until the desired separation, typically measured by hematocrit, has been achieved. Doing so reduces the cost of the disposable cassette without reducing the effectiveness of the system. Recirculation can be achieved, for example, using appropriate pinch valves and the main blood pump or with the aid of a separate blood recirculation pump. Recirculation may, or may not, involve the use of a recirculated blood reservoir.
A primary advantage of the invention is the interchangeability of the components and the ease of modifying the invention to accommodate different blood processing systems. For example, it is often possible to modify the blood processing system to accomplish different tasks, for example blood collection, autotransfusion, thawed blood processing, or red cell washing, by simply modifying the specific computer program used to run the controller, and changing the number and types of bags, where the bags are hung and how the bags are hooked up to the remainder of the system. Only the disposable cassette will usually be specially constructed for a particular procedure or process. Because the same general system can be used for a wide variety of specific blood processing tasks, economies of scale, and thus lower user cost, can be achieved.
Another advantage of, and a further aspect of, the invention is that the cassette can be easily tested to ensure that it is leak-free, which is a very necessary attribute for the system. This can be accomplished simply by pressurizing the flow channels and determining the rate of any drop-off in pressure. Any unacceptable cassettes can be either discarded or reworked prior to being shipped to solve the problem.
It is important that the system not be run when, for example, the source of blood or of a supplemental fluid, such as saline or anticoagulant, is not connected to flow channels of the cassette, or when the source is empty, or when a valve is incorrectly closed, or when a line is crimped. Various detectors non-invasively provide the necessary signals to the controller so that the controller can shut down pumping by halting the rotation of the roller assemblies and/or closing pinch valves should any of these problems occur. Doing so helps reduce the negative results of operator error or product failure.
It is important that the cassette be positioned so that tubing is not improperly engaged in the latched position. It is important to provide structure to accomplish this and, at the same time, properly align the tubing on the cassette relative to the roller assemblies and the pinch elements for proper operation. This is aided by ensuring that the cassette is properly positioned in the cassette holder so that with the cassette assembly in the use position and the door in the latched position, all elements are properly aligned. The proper positioning of the cassette in the cassette holder is aided by the fact that gravity helps keep the cassette properly and fully engaged within and supported by the cassette holder. Also, or as an alternative, appropriate guide elements, such as tapered pins, extending from the housing or the cassette can be used to engage appropriately located guide holes in the cassette or the housing when the cassette assembly is in the use position.
Accurate but non-invasive pressure measurements taken along the flow channels are important to, for example, ensure correct and safe pressure levels and to control fluid flow rates by monitoring pressure drops across a pressure drop device such as a laminar flow tube. This can be achieved using sealed diaphragm pressure access ports along the flow channel; the pressures at such ports are preferably coupled to a pressure sensor which provides a pressure signal to the controller for each pressure access port monitored. Fluidly coupling the pressure sensor and the pressure access ports is preferably automatically made as the cassette is secured into its use position and the door is placed into its latched position.
It is also important to add anticoagulant to the blood and mix the two well. When blood is recirculated and stored in a recirculation reservoir, it is important in some uses to ensure that the blood is thoroughly mixed with inlet blood entering the reservoir along with a saline or other solution for effective red cell washing. This can be accomplished by automatically and mechanically manipulating the bag-type reservoir by, for example, flexing, kneading or punching the bag-type reservoir. Such mechanical manipulation of a bag-type reservoir simply and thoroughly mixes the contents of the bag but without any physical contact with the blood. Thorough mixing can, for example, also be accomplished by pumping from one reservoir into another reservoir or through the use of mechanical stirrers.
Mechanical bag manipulators preferably act on vertically-hung bags so that the contents of the bags can be mixed while processing without the need for special supports or alignments of the bags. While vertically-hung bags can have their contents mixed by shaking the entire bag support, this is not usually preferred because of problems caused by the shaking, such as loosening of fittings, noise, etc.